The acute administration of cocaine (15-30 mg/kg) consistantly increases substance P in dorsal raphe with a corresponding decrease in 5-HT levels. When rats are treated with 5-hydroxytryptophan (5-HTP) along with the decarboxylase inhibitor, RO4-4602, 5-HT content in PM increases with a significant decrease in SP level in dorsal raphe. But when cocaine, 5-HTP and RO4-4602 are administered simultaneously, the changes in 5-HT and SP levels are attenuated. These results suggest that there is a specific interaction between the neurotransmitters substance P and 5-HT in the dorsal raphe area.